Cargando…

Gastrodin Ameliorates Motor Learning Deficits Through Preserving Cerebellar Long-Term Depression Pathways in Diabetic Rats

Cognitive dysfunction is a very severe consequence of diabetes, but the underlying causes are still unclear. Recently, the cerebellum was reported to play an important role in learning and memory. Since long-term depression (LTD) is a primary cellular mechanism for cerebellar motor learning, we aime...

Descripción completa

Detalles Bibliográficos
Autores principales: Deng, Cheng-Kun, Mu, Zhi-Hao, Miao, Yi-He, Liu, Yi-Dan, Zhou, Lei, Huang, Yong-Jie, Zhang, Fan, Wang, Yao-Yi, Yang, Zhi-Hong, Qian, Zhong-Yi, Wang, Xie, Guo, Jia-Zhi, Zhang, Mei-Yan, Liao, Xin-Yu, Wan, Qi, Lu, Di, Zou, Ying-Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883220/
https://www.ncbi.nlm.nih.gov/pubmed/31824244
http://dx.doi.org/10.3389/fnins.2019.01239
_version_ 1783474320336486400
author Deng, Cheng-Kun
Mu, Zhi-Hao
Miao, Yi-He
Liu, Yi-Dan
Zhou, Lei
Huang, Yong-Jie
Zhang, Fan
Wang, Yao-Yi
Yang, Zhi-Hong
Qian, Zhong-Yi
Wang, Xie
Guo, Jia-Zhi
Zhang, Mei-Yan
Liao, Xin-Yu
Wan, Qi
Lu, Di
Zou, Ying-Ying
author_facet Deng, Cheng-Kun
Mu, Zhi-Hao
Miao, Yi-He
Liu, Yi-Dan
Zhou, Lei
Huang, Yong-Jie
Zhang, Fan
Wang, Yao-Yi
Yang, Zhi-Hong
Qian, Zhong-Yi
Wang, Xie
Guo, Jia-Zhi
Zhang, Mei-Yan
Liao, Xin-Yu
Wan, Qi
Lu, Di
Zou, Ying-Ying
author_sort Deng, Cheng-Kun
collection PubMed
description Cognitive dysfunction is a very severe consequence of diabetes, but the underlying causes are still unclear. Recently, the cerebellum was reported to play an important role in learning and memory. Since long-term depression (LTD) is a primary cellular mechanism for cerebellar motor learning, we aimed to explore the role of cerebellar LTD pathways in diabetic rats and the therapeutic effect of gastrodin. Diabetes was induced by a single injection of streptozotocin into adult Sprague–Dawley rats. Motor learning ability was assessed by a beam walk test. Pathological changes of the cerebellum were assessed by Hematoxylin-Eosin (HE) and Nissl staining. Cellular apoptosis was assessed by anti-caspase-3 immunostaining. Protein expression levels of LTD pathway-related factors, including GluR2, protein kinase C (PKC), NR2A, and nNOS, in the cerebellar cortex were evaluated by western blotting and double immunofluorescence. The NO concentration was measured. The cellular degeneration and the apoptosis of Purkinje cells were evident in the cerebellum of diabetic rats. Protein expression levels of GluR2 (NC9W: 1.26 ± 0.12; DM9W + S: 0.81 ± 0.07), PKC (NC9W: 1.66 ± 0.10; DM9W + S: 0.58 ± 0.19), NR2A (NC9W: 1.40 ± 0.05; DM9W + S: 0.63 ± 0.06), nNOS (NC9W: 1.26 ± 0.12; DM9W + S: 0.68 ± 0.04), and NO (NC9W: 135.61 ± 31.91; DM9W + S: 64.06 ± 24.01) in the cerebellum were significantly decreased in diabetic rats. Following gastrodin intervention, the outcome of motor learning ability was significantly improved (NC9W: 6.70 ± 3.31; DM9W + S: 20.47 ± 9.43; DM9W + G: 16.04 ± 7.10). In addition, degeneration and apoptosis were ameliorated, and this was coupled with the elevation of the protein expression of the abovementioned biomarkers. Arising from the above, we concluded that gastrodin may contribute to the improvement of motor learning by protecting the LTD pathways in Purkinje cells.
format Online
Article
Text
id pubmed-6883220
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-68832202019-12-10 Gastrodin Ameliorates Motor Learning Deficits Through Preserving Cerebellar Long-Term Depression Pathways in Diabetic Rats Deng, Cheng-Kun Mu, Zhi-Hao Miao, Yi-He Liu, Yi-Dan Zhou, Lei Huang, Yong-Jie Zhang, Fan Wang, Yao-Yi Yang, Zhi-Hong Qian, Zhong-Yi Wang, Xie Guo, Jia-Zhi Zhang, Mei-Yan Liao, Xin-Yu Wan, Qi Lu, Di Zou, Ying-Ying Front Neurosci Neuroscience Cognitive dysfunction is a very severe consequence of diabetes, but the underlying causes are still unclear. Recently, the cerebellum was reported to play an important role in learning and memory. Since long-term depression (LTD) is a primary cellular mechanism for cerebellar motor learning, we aimed to explore the role of cerebellar LTD pathways in diabetic rats and the therapeutic effect of gastrodin. Diabetes was induced by a single injection of streptozotocin into adult Sprague–Dawley rats. Motor learning ability was assessed by a beam walk test. Pathological changes of the cerebellum were assessed by Hematoxylin-Eosin (HE) and Nissl staining. Cellular apoptosis was assessed by anti-caspase-3 immunostaining. Protein expression levels of LTD pathway-related factors, including GluR2, protein kinase C (PKC), NR2A, and nNOS, in the cerebellar cortex were evaluated by western blotting and double immunofluorescence. The NO concentration was measured. The cellular degeneration and the apoptosis of Purkinje cells were evident in the cerebellum of diabetic rats. Protein expression levels of GluR2 (NC9W: 1.26 ± 0.12; DM9W + S: 0.81 ± 0.07), PKC (NC9W: 1.66 ± 0.10; DM9W + S: 0.58 ± 0.19), NR2A (NC9W: 1.40 ± 0.05; DM9W + S: 0.63 ± 0.06), nNOS (NC9W: 1.26 ± 0.12; DM9W + S: 0.68 ± 0.04), and NO (NC9W: 135.61 ± 31.91; DM9W + S: 64.06 ± 24.01) in the cerebellum were significantly decreased in diabetic rats. Following gastrodin intervention, the outcome of motor learning ability was significantly improved (NC9W: 6.70 ± 3.31; DM9W + S: 20.47 ± 9.43; DM9W + G: 16.04 ± 7.10). In addition, degeneration and apoptosis were ameliorated, and this was coupled with the elevation of the protein expression of the abovementioned biomarkers. Arising from the above, we concluded that gastrodin may contribute to the improvement of motor learning by protecting the LTD pathways in Purkinje cells. Frontiers Media S.A. 2019-11-22 /pmc/articles/PMC6883220/ /pubmed/31824244 http://dx.doi.org/10.3389/fnins.2019.01239 Text en Copyright © 2019 Deng, Mu, Miao, Liu, Zhou, Huang, Zhang, Wang, Yang, Qian, Wang, Guo, Zhang, Liao, Wan, Lu and Zou. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Deng, Cheng-Kun
Mu, Zhi-Hao
Miao, Yi-He
Liu, Yi-Dan
Zhou, Lei
Huang, Yong-Jie
Zhang, Fan
Wang, Yao-Yi
Yang, Zhi-Hong
Qian, Zhong-Yi
Wang, Xie
Guo, Jia-Zhi
Zhang, Mei-Yan
Liao, Xin-Yu
Wan, Qi
Lu, Di
Zou, Ying-Ying
Gastrodin Ameliorates Motor Learning Deficits Through Preserving Cerebellar Long-Term Depression Pathways in Diabetic Rats
title Gastrodin Ameliorates Motor Learning Deficits Through Preserving Cerebellar Long-Term Depression Pathways in Diabetic Rats
title_full Gastrodin Ameliorates Motor Learning Deficits Through Preserving Cerebellar Long-Term Depression Pathways in Diabetic Rats
title_fullStr Gastrodin Ameliorates Motor Learning Deficits Through Preserving Cerebellar Long-Term Depression Pathways in Diabetic Rats
title_full_unstemmed Gastrodin Ameliorates Motor Learning Deficits Through Preserving Cerebellar Long-Term Depression Pathways in Diabetic Rats
title_short Gastrodin Ameliorates Motor Learning Deficits Through Preserving Cerebellar Long-Term Depression Pathways in Diabetic Rats
title_sort gastrodin ameliorates motor learning deficits through preserving cerebellar long-term depression pathways in diabetic rats
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883220/
https://www.ncbi.nlm.nih.gov/pubmed/31824244
http://dx.doi.org/10.3389/fnins.2019.01239
work_keys_str_mv AT dengchengkun gastrodinamelioratesmotorlearningdeficitsthroughpreservingcerebellarlongtermdepressionpathwaysindiabeticrats
AT muzhihao gastrodinamelioratesmotorlearningdeficitsthroughpreservingcerebellarlongtermdepressionpathwaysindiabeticrats
AT miaoyihe gastrodinamelioratesmotorlearningdeficitsthroughpreservingcerebellarlongtermdepressionpathwaysindiabeticrats
AT liuyidan gastrodinamelioratesmotorlearningdeficitsthroughpreservingcerebellarlongtermdepressionpathwaysindiabeticrats
AT zhoulei gastrodinamelioratesmotorlearningdeficitsthroughpreservingcerebellarlongtermdepressionpathwaysindiabeticrats
AT huangyongjie gastrodinamelioratesmotorlearningdeficitsthroughpreservingcerebellarlongtermdepressionpathwaysindiabeticrats
AT zhangfan gastrodinamelioratesmotorlearningdeficitsthroughpreservingcerebellarlongtermdepressionpathwaysindiabeticrats
AT wangyaoyi gastrodinamelioratesmotorlearningdeficitsthroughpreservingcerebellarlongtermdepressionpathwaysindiabeticrats
AT yangzhihong gastrodinamelioratesmotorlearningdeficitsthroughpreservingcerebellarlongtermdepressionpathwaysindiabeticrats
AT qianzhongyi gastrodinamelioratesmotorlearningdeficitsthroughpreservingcerebellarlongtermdepressionpathwaysindiabeticrats
AT wangxie gastrodinamelioratesmotorlearningdeficitsthroughpreservingcerebellarlongtermdepressionpathwaysindiabeticrats
AT guojiazhi gastrodinamelioratesmotorlearningdeficitsthroughpreservingcerebellarlongtermdepressionpathwaysindiabeticrats
AT zhangmeiyan gastrodinamelioratesmotorlearningdeficitsthroughpreservingcerebellarlongtermdepressionpathwaysindiabeticrats
AT liaoxinyu gastrodinamelioratesmotorlearningdeficitsthroughpreservingcerebellarlongtermdepressionpathwaysindiabeticrats
AT wanqi gastrodinamelioratesmotorlearningdeficitsthroughpreservingcerebellarlongtermdepressionpathwaysindiabeticrats
AT ludi gastrodinamelioratesmotorlearningdeficitsthroughpreservingcerebellarlongtermdepressionpathwaysindiabeticrats
AT zouyingying gastrodinamelioratesmotorlearningdeficitsthroughpreservingcerebellarlongtermdepressionpathwaysindiabeticrats